Ventricular chamber dilatation and myocardial hypertrophy are important compensatory responses that accompany a volume overload state. However, at some point in time, and despite continued dilatation, the heart fails. The answer as to why the heart fails with volume overload may be obtained from an investigation into the structural basis for dilatation and, in particular, the cardiac interstitium and fibrillar collagen which are responsible for maintaining myocyte alignment, resisting myocardial deformation, preventing myocyte slippage and promoting the efficient transduction of myocyte-generated force to the ventricular chamber. If this extracellular matrix is "inadequate", either because collagen fibers have been disrupted or because its tensile strength is reduced, then changes in the size and shape of the ventricle could occur together with myocyte slippage and muscle fiber realignment. There is both morphologic and biochemical evidence to indicate that one or both these events is operative in the structural remodeling of the myocardium that is associated with pressure overload hypertrophy. This remains to be demonstrated in volume overload and dilatation. Accordingly, it is the overall hypothesis of this proposal that in acute or chronic volume overload an "inadequate" collagen matrix is responsible for structural and architectural remodeling of the myocardium, including chamber dilatation, and this leads to impaired myocardial force generation and heart failure. Toward this end, we propose to examine the temporal response in myocyte density, muscle fiber alignment, chamber size and shape, the concentration, composition, nature and integrity of fibrillar collagen and passive and active myocardial stiffness and ventricular resistance in animals with a sudden or gradual volume overload secondary to either aortic valve incompetence or chronic rapid ventricular pacing, respectively. The following specific aims will be addressed: 1) to determine the initial and subsequent nature of ventricular muscle, collagen and chamber remodeling that occur in the normal heart in response to either an acute or more gradual volume overload; 2) to determine if collagen fiber disruption or an excess amount of type III collagen prior to a volume overload will accelerate the sequence of the structural and architectural remodeling of the myocardium, including chamber dilatation and the appearance of heart failure; and 3) to determine if an increase in collagen concentration prior to a volume overload will protect the myocardium from structural dilatation and the appearance of heart failure or if this would instead reduce ventricular capacitance and more quickly lead to heart failure.